Inhibitors of catecholamine metabolizing enzymes cause changes in S-adenosylmethionine and S-adenosylhomocysteine in the rat brain.
Previous studies have shown that the biochemical changes that occur in parkinsonism are associated with disturbances in methylation reactions. Therefore, our hypothesis was that MAO and COMT inhibitors, which inhibit the metabolism of dopamine, might affect the methylation reaction. In the present study, we analyzed levels of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) in brain homogenates from rats which had received a one-week treatment with tolcapone or phenelzine, inhibitors of COMT and MAO, respectively. Tolcapone treatment caused an increase in the levels of SAM (130% as compared with control animals, p < 0.001). In animals treated with phenelzine, the SAM levels were 78% of those of the controls (p < 0.05). SAH levels were slightly increased (115% as compared with controls, p < 0.05) in the phenelzine group, while they were unchanged in the tolcapone treated animals. Treatment with tolcapone decreased the catalytic activity of methionine adenosyltransferase (MAT) (from 15.4 +/- 1.6 to 11.3 +/- 1.4 pmol mg-1 min-1, p < 0.0001) while phenelzine treatment had no significant effect. In addition the transmethylation ratio (SAM/SAH) were significantly increased with tolcapone (120%, p < 0.05) and decreased with phenelzine (71%, p < 0.05) as compared to the controls. The essential finding of this paper was that brain SAM levels were reduced by MAO inhibition and enhanced by COMT inhibition.
Yassin
M S
MS
Department of Medical Pharmacology, Uppsala University, Sweden.
Cheng
H
H
Ekblom
J
J
Oreland
L
L
D000818:Animals; D001577:Benzophenones / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D065098:Catechol O-Methyltransferase Inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008716:Methionine Adenosyltransferase / Q000378:metabolism; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009596:Nitrophenols; D010624:Phenelzine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012435:S-Adenosylhomocysteine / Q000378:metabolism*; D012436:S-Adenosylmethionine / Q000378:metabolism*; D000077867:Tolcapone
D001577:Benzophenones; D065098:Catechol O-Methyltransferase Inhibitors; D004791:Enzyme Inhibitors; D008996:Monoamine Oxidase Inhibitors; D009596:Nitrophenols; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D000077867:Tolcapone; D008995:Monoamine Oxidase; D008716:Methionine Adenosyltransferase; D010624:Phenelzine